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ITF2357 (Givinostat)HDAC inhibitor

ITF2357 (Givinostat)

Catalog No. A4093
Size Price Stock Qty
Evaluation Sample $28.00 In stock
5mg $110.00 In stock
10mg $190.00 In stock
50mg $590.00 In stock
200mg $1,490.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

ITF2357 (Givinostat)

Related Biological Data

ITF2357 (Givinostat)

Related Biological Data

ITF2357 (Givinostat)

Biological Activity

Description Givinostat (ITF2357) is a potent inhibitor of HDAC for maize HD2, HD1B and HD1A with IC50 of 10 nM, 7.5 nM and 16 nM, respectively.
Targets HDAC          
IC50 7.5 to 16 nM          

Protocol

Cell experiment: [1]

Cell lines

PBMC cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reacting condition

100 nM, 24 hours for hyperacetylation

Applications

To test the acetylation ability of ITF2357, rested PBMCs were preincubated with the inhibitor for 1 h at 37° C and then stimulated with LPS. After 3, 6, and 24 h, extracts of the cell pellets were made and the acetylated lysines were determined in total cellular extracts. After 3 h of incubation with LPS in the presence of ITF2357, hyperacetylation is clearly present. However, a greater duration of hyperacetylation up to 24 h was observed in cells exposed to ITF2357.

Animal experiment: [1]

Animal models

BALB/C and C57BL/6 mice

Dosage form

Gavage, 5 mg/kg (BALB/C mice) Gavage, 1 or 10 mg/kg (C57BL/6 mice)

Application

Mice were given 100 µL water or ITF2357 (5 mg/kg) by gavage and, after 1 h, injected intravenously with 200 µg/mouse of ConA. Mice were bled 24 h later for evaluation of serum ALT levels. ITF2357 pretreatment reduced more than 80% of the ALT levels. A dose of 1 mg/kg ITF2357 was as effective as a dose of 10 mg/kg in reducing ConA hepatitis as measured by ALT levels.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Leoni F, Fossati G, Lewis E C, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Molecular Medicine, 2005, 11(1-12): 1.

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Chemical Properties

Cas No. 732302-99-7 SDF Download SDF
Synonyms ITF-2357
Chemical Name (6-((diethylamino)methyl)naphthalen-2-yl)methyl (4-(hydroxycarbamoyl)phenyl)carbamate hydrochloride hydrate
Canonical SMILES CCN(CC)CC1=CC2=C(C=C(COC(NC3=CC=C(C(NO)=O)C=C3)=O)C=C2)C=C1.O.Cl
Formula C24H27N3O4.HCl.H2O M.Wt 475.97
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Research Update

1. Inhibition of HDAC activity by ITF2357 ameliorates joint inflammation and prevents cartilage and bone destruction in experimental arthritis. Mol Med. 2011 May-Jun;17(5-6):391-6. doi: 10.2119/molmed.2011.00058. Epub 2011 Feb 11.
Abstract
In models of arthritis, ITF2357, an HDACi, reduced joint swelling and cell influx into the joint cavity, improved the chondrocyte metabolic function, decreased production of proinflammatory cytokines, ameliorates the severity scores and prevented bone destruction.
2. Class I and II histone deacetylase inhibition by ITF2357 reduces SLE pathogenesis in vivo. Clin Immunol. 2014 Mar;151(1):29-42. doi: 10.1016/j.clim.2014.01.002. Epub 2014 Jan 15.
Abstract
ITF2357, an inhibitor of class I and II HDAC, decreased renal disease, inflammatory cytokines and Th17 phenotype in NZB/W mice; while it increased the percentage of Tregs and Foxp3 acetylation.
3. The oral histone deacetylase inhibitor ITF2357 reduces cytokines and protects islet β cells in vivo and in vitro. Mol Med. 2011 May-Jun;17(5-6):369-77. doi: 10.2119/molmed.2010.00152. Epub 2010 Dec 22.
Abstract
ITF2357 is an HDAC inhibitor that inhibits production of nitrite, TNFα and IFNγ in peritoneal macrophages and splenocytes. ITF2357 normalized STZ-induced hyperglycemia in mice returning serum nitrite levels to nondiabetic values, improving islet and increasing glucose clearance; while it increased islet cell viability, enhanced insulin secretion, inhibited MIP-1α and MIP-2 release, reduced nitric oxide production and decreased apoptosis rates in vitro.
4. The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro. J Acquir Immune Defic Syndr. 2010 May 1;54(1):1-9. doi: 10.1097/QAI.0b013e3181d3dca3.
Abstract
ITF2357, an HDAC inhibitor, has been evaluated for its efficacy on HIC-1 expression from latently infected cells and its effect on the surface expression of CXCR4 and CCR5.
5. Effects of the histone deacetylase inhibitor ITF2357 in autoinflammatory syndromes. Mol Med. 2011 May-Jun;17(5-6):363-8. doi: 10.2119/molmed.2011.00039. Epub 2011 Jan 25.
Abstract
ITF2357, an HDAC inhibitor, was used to treatment patients with autoflammatory syndrome, including 1 patient with TRAPS, 3 patients with HIDS and 4 patients with Schnitzler syndrome, in a pilot study where ITF2357-induced partial response was only observed in patients with Schnitzler syndrome.

Background

ITF2357, also known as givinostat, is a potent inhibitor of both class I and class II histone deacetylase (HDAC) as well as a potent inhibitor of hematopoietic colony formation by JAKEV617F-bearing progenitor cells from chronic myeloproliferative neoplasms in vitro. Previous studies has shown that ITF2357 induces apoptosis of multiple myeloma (MM) and acute myelogenous leukemia (AML) cells following induction of p21 and down-modulation of Bcl-2 and Mcl-1 proteins and inhibits the production of pro-inflammatory cytokines (such as IL-1, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) by peripheral blood mononuclear cells as well as the production of IL-6 and vascular endothelium growth factor (VEGF) by mesenchymal stromal cells.

Reference

Katia Todoerti, Valentina Barbui, Olga Pedrini, Marta Linett, Gianluca Fossati, Paolo Mascagni, Alessandro Rambaldi, Antonino Neri, Martino Introna, Luigia Lombardi, and Josee Golay. Pleiotropi anti-myeloma activity of ITF2357: inhibition of interleukin-6 receptor signaling and repression of miR-19a and miR-19b. Haematologica 2010; 95(2): 260-269